The Presence Of Hepatitis B Envelope Antibody In Patients Who Have Been Previously Screened For The Surface Antigen

The Presence Of Hepatitis B Envelope Antibody In Patients Who Have Been Previously Screened For The Surface Antigen

Abstract

This study determined the presence of Hepatitis B surface Antigen (HBsAg) among patients who have previosly been screened for the antigen attending Aminu Kano Teaching Hospital and Hasiya Bayero Paediatric Hospital Kano. It also determined some sociodemographic factors and some possible risk factors associated with acquiring the viruses. A total of 460 blood samples were collected and analysed for HPVB19 IgG by ELISA and HBsAg using the rapid test strip. Prevalence of 41.5% (191/460) and 8.5% (39/460) was found for Hepatitis B respectively. For HPVB19 IgG the presence increased with age with the highest prevalence (51%) recorded among patients who have previosly been screened for the antigen ≥51 years old while the lowest was among those < 1 year old (χ2=13.130, df=6, P=0.04). Higher prevalence was found in female (42.6%:98/230) than male patients (40.4%:93/230), though not statistically significant. With respect to occupation the highest seropositivity was observed among farmers (64.2%:18/28) while the lowest was among retired persons (27.2%:3/11). There was significantly associated between level of formal education attained and HPVB19 (χ2 =10.363, df=4, P=0.03) and number of persons living in a house (χ2 =14.303, df=1, P=0.00) respectively but no statistically significant association was observed with marital status and type of residence (P=0.3, P=0.5) respectively. History of transfusion was an important risk factor for HPVB19 transmission (OR=2.0:1; P=0.08). the presence among pregnant female patients was 41.5% (17/41). Despite the availability of a vaccine a HBsAg prevalence rate of 8.5% (39/460) was reported in this study. Patients in age group 21-30 years old had the highest prevalence of 15.5% (16/103) but the virus was not detected in patients <1 year old and seropositivity was significantly associated with age (χ 2=16.620, df=6, P=0.01). Prevalence in male patients (8.2%:19/230) did not differ significantly from prevalence in female (8.7%:20/230). In relation to marital status, level of education, type of residence and number of persons living in a house, there was no statistically significant association with Hepatitis B Virus. Similarly there was no statistically significant relationship between blood transfusion, history of jaundice, organ transplant and HBV infection among the study population. Overall, age was a significant factor in the presence of both viruses in the population.

Chapter One

Introduction

A virus is a small infectious agent having a simple acellular organization with a nucleic acid and aprotein coat.It lacks independent metabolism and replicate only within living hosts. A virus invades living cells and uses its chemical machinery to keep itself alive and replicate in the host. It may reproduce with fidelity or with errors (mutations); this ability to mutate is responsible for the ability of some viruses to change slightly in each infected person, making treatment difficult. Viruses cause many human infections and are also responsible for a number of rare diseases. The human diseases they cause may affect different organs or parts of the body. An inflammation of the liver is often referred to by a general term called Hepatitis, which is often caused by a variety of viruses which include hepatitis A, B, C, D and E. Of the viral causes of hepatitis, there are few of greater global importance than hepatitis B (Ganem et al, 2001).

The hepatitis B virus (HBV) belongs to the family Hepadnaviridae, which consists of hepatotropic DNA viruses. The family of Hepadnaviruses comprises members recovered from animal species including the woodluck hepatitis virus (WHV), the ground squirrel hepatitis virus (GSHV), and the duck HBV. Common features of all of these viruses are enveloped virions containing 3 to 3.3 kb of relaxed circular partially duplex DNA and have reverse transcriptase activities. Hepadnaviruses show narrow host ranges, growing only in species close to the natural host, like gibbons, African green monkeys, rhesus monkeys and woolly monkeys (Gitlin,1997).The Hepatitis virus belongs to the genus Hepadnavirus. It is a 42nm partially double stranded DNA virus, composed of a 27nm nucleic acid core (HBcAg), a DNA polymerase reverse transcriptase, surrounded by an outer lipoprotein coat (called envelope) containing the surface antigen (HBsAg)that play a major role in the diagnosis of HBV infection (Ganem et al; 2001; Gitlin,1997). The genome consists of a partially double-stranded circular DNA molecule of about 3200 base pairs in length with known sequence as well as genetic organization. Virion particles are identical to the virion ‘tails’- they vary in length and have a mean diameter of about 22nm. They sometimes display regular, non-helical transverse striations.

The viral DNA polymerase-reverse transcriptase is encoded by the polymerase gene [P] and is of central importance for viral replication. Different from all known mammalian DNA viruses, hepadnaviruses replicate via reverse transcription of a RNA intermediate (Summerset al.,1982), the pregenomic RNA, which is a strategy central to the life cycle of RNA retroviruses. Similarities and differences between retroviral and hepadnaviral replication have been defined (Nassal, 1999). Based on the unique replication cycle of HBV, antiviral therapeutic strategies aimed at the reverse transcription of HBV RNA or at HBV reverse transcriptase have been successfully used as antivirals to treat HBV infection (Feld, 2002).

The prevalence of HBV infection varies in different countries or regions in the world as well as in different ethnic groups. HBV endemicity has been classified into three categories, high (>8%), intermediate (2–8%), and low (<2%), depending on the prevalence of hepatitis B surface antigen (HBsAg) seropositivity. The highly endemic areas in the world include East and Southeast Asia, the Pacific, sub-Saharan Africa(Nigeria inclusive), and parts of southern Europe. In North America, and western and northern Europe, HBV infection is relatively rare, with a prevalence rate of around 0.1%.Hepatitis B virus (HBV) infection is a serious global health problem, with 2 billion people infected world-wide, and 350 million suffering from chronic HBV infection. HBV is the 10th leading cause of death worldwide, HBV infections result in 600 000 deaths annually (Ott et al 2012). 1.2 million deaths per year are caused by chronic hepatitis, cirrhosis, and hepatocellular carcinoma; the last accounts for 320 000 deaths per year (WHO, 2000). In Western countries, the disease is relatively rare and acquired primarily in adulthood, whereas in Asia and most of Africa, chronic HBV infection is common and usually acquired perinatally or in childhood.

The whole of Africa is regarded as highly endemic, coming only behind Asia. Although overall Africa is considered a high endemic area with 7–26% prevalence of HBsAg, Tunisia, Morocco, and Zambia have intermediate endemicity (Andre, 2000). In West Africa, countries like Senegal and Gambia have over 90% of their populations exposed to and becoming infected with HBV during their lives (Edmund WJ. et al., 1996). In Nigeria, not less than 23 million people are estimated to be infected with HBV (Bukola, 2015), making Nigeria one of the countries with the highest incidence of HBV infection in the world.

Hepatitis B is caused by hepatitis B virus. The virus interferes with the functions of the liver while replicating in hepatocytes. The immune system is then activated to produce a specific reaction to combat and possibly eradicate the infectious agent. As a consequence of pathological damage, the liver becomes inflamed. HBV may cause up to 80 per cent of all cases of hepatocellular carcinoma (HCC) worldwide, second only to tobacco among known human carcinogens (WHO, 2001). Most people do not experience any symptoms during the acute infection phase. However, some people have acute illness with symptoms that last several weeks, including yellowing of the skin and eyes (jaundice), dark urine, extreme fatigue, nausea, vomiting and abdominal pain. In some people, the hepatitis B virus can also cause a chronic liver infection that can later develop into cirrhosis of the liver or liver cancer (WHO, 2014).

Susceptibility to HBV infection is general. Only people who have been vaccinated successfully or have developed anti-HBs antibodies after HBV infection are immune to HBV infection. Persons with congenital or acquired immunodeficiency including HIV infection, those with immunosuppression including those with lymphoproliferative disease, patients treated with immunosuppressive drugs including steroids and by maintenance haemodyalisis are more likely to develop persistent infection with HBV.

Hepatitis B can be spread by

1. Unprotected sex
2. Sharing IV drug needles
3. Living in a household with an infected person
4. An infected mother to her newborn child at birth
5. Sharing earrings, razors, or toothbrushes with an infected person
6. Unsterilized needles, including tattoo or piercing needles
7. Human bites (www.hepb.org).

People are most at risk for hepatitis B if they

1. Are born to mothers who are infected with HBV
2. Live in close household contact with a chronically infected individual
3. Adopt a child from a country where HBV is prevalent
4. Have unprotected sex or have more than one sexual partner in a six month period
5. Have ever been diagnosed with a sexually transmitted disease (STD)
6. Are men who have sex with men
7. Share needles and syringes
8. Are health care provider or emergency responder with possible contact with bodily fluids
9. Are a patient on kidney dialysis
10. Live or work in an institutional setting, such as a prison or group home (www.hepb.org).

Diagnosis of hepatitis is made by biochemical assessment of liver function. Initial laboratory evaluation should include: total and direct bilirubin, ALT (alanine transaminase,) AST (aspartate aminotransferase), alkaline phosphatase, prothrombin time, total protein albumin, globulin, complete blood count, and coagulation studies(Hollingeret al.,2001). Diagnosis is confirmed by demonstration of specific antigens and/or antibodies.

There is yet no treatment for acute HBV infection, but it is a vaccine-preventable infection. Several vaccines have been used in the prevention of this infection, the prominent ones including Lamivudine, Adefovir, Dipivoxil, Famvir, FTC, Ritonavir, Theradigm-HBV, Ganciclovir (Hadziyannis et al.,1999).

1.1 Statement of Research Problem

In general, infection with Parvovirus B19 may be mild, with most of the infections remaining asymptomatic and self-limiting but it can cause significant morbidity and occasional persistent infections or mortality in humans particularly in pregnant women or those who are immunocompromised. Severe symptoms such as acute or persistent arthropathies, critical failures of red cell production, hydrops foetalis, foetal loss, myocarditis or hepatitis (Kaufmann et al., 2004) leading to serious complication or health problems can be linked to the virus. While most individuals experience transient infection in childhood, there is mounting evidence that the virus persists following acute infection in certain tissue types, including liver, synovium, and skin (Eis-Hübinger et al., 2001; Soderlund-Venermo et al., 2002; Norja et al., 2006; Norja et al., 2008).

Hepatitis B virus is endemic in Nigeria (Opaleye et al., 2011). The viral infection and its sequelae have become significant in our environment, most importantly owing to the high mortality rate associated with liver cirrhosis and hepatocellular carcinoma (Agbede et al., 2007). Recent finding showed that HPVB19 is involved possibly in the disease progression of Asian patients infected with hepatitis B and that there is an association between infection with HPVB19 and the clinical course of HBV-associated liver disease (Toan et al., 2006). It has also been reported that B19-DNA could be detected in the liver-tissues of 10/30 (30%) patients with HBV and or HCV infection (Wong et al., 2003). However, the role of this virus as a possible pathogen causing fulminant, chronic, or acute hepatitis is still controversial (Wong et al., 2003; Hsu et al., 2005; Toan et al., 2006). Since receptors for B19 are expressed in the kidney and the heart, its role in myocarditis, liver and renal transplant complications and/or rejection should not be underestimated (Shashwat et al., 2005). Therefore, the virus may play a role in aggravating the liver disease resulting from hepatitis B and C virus infection as reported previously (Hsu et al., 2005).

1.4 Objectives of Study

1. To determine the presence of Hepatitis B surface antigen among patients who have previously been screened for the antigen attending some hospitals in Kano Metropolis.
2. To determine the effect of some sociodemographic variables on the seropositivity of individuals to Hepatitis B.
3. To determine the possible risk factors associated with Hepatitis B infection.
4. To determine the percentage of women of childbearing age among the study population who are susceptible to HPVB19.

Chapter Five

Discussion of Findings, Conclusion and Recommendation

5.1 Discussion

The prevalence of HPVB19 IgG antibody obtained in this study was 41.5% which suggests that HPVB19 infection is endemic in Kano metropolis. This result is almost similar to the prevalence of 39.5% reported in Jos (Girei et al., 2010) and 39.9% in India but lower than the prevalence of 85.4% reported in Zaria (Ujo et al., 2012). Prevalence ranges of 60-70% have been reported from developed countries such as England (Cohen and Buckley, 1988) and lower prevalence of 16.2% has been reported in Singapore (Matsunag et al., 1994). These discrepancies could be due to differences in the specificity and sensitivity of the assays used. Hepatitis B infection infection has been reported in many countries around the world and the seropositive rate varies by location (Salimi et al., 2008). However the presence obtained in this study is within the range of 35%-70% reported from different serosurveys among the general healthy population in different regions of the world (Kelly et al., 2000).

Several studies in different regions of the world have identified different socio-demographic variables like age, gender, socio-economic status and environmental conditions as risk factors for acquisition of parvovirus B19 infection (Alao et al., 2010). For example, age has been consistently shown to be a major predictor of anti parvovirus B19 IgG seropositivity (Ooi et al., 2002; Mazyar and Abdolvahab, 2007; Alao et al., 2010).

This study showed that seropositivity increased with age. This increasing seropositivity with increasing age is consistent with the work of Girei in Jos (Girei et al., 2010) and those reported in other countries (Ooi et al., 2002; Salimi et al., 2008;

Kishore et al., 2010). For Parvovirus B19, seropositivity implies immunity, because increase in the presence with age means that the proportion of individuals susceptible to parvovirus B19 decreases with age (Gilbert et al., 2005; Salimi et al., 2008).

However, the finding contrasts the result of Ujo and colleagues (2012) who reported that seropostivity did not increase with age. This could be due to the fact their study was carried out in children with sickle cell disease whereas the present study was carried out among the general population aged from 0-70 years.

The prevalence obtained among patients who have previosly been screened for the antigen age group >51 years in this study is similar to 50% found in India (Kishore et al., 2010) and slightly lower than 55% reported in Malaysia (Ooi et al., 2002) for the same age group. This difference could be due to dwindling immune response in the elderly, as a result of natural waning of antibodies with time as the antibodies could have decreased to a level beneath the detection limit of the test used here.

This study however did not demonstrate any association between gender and seropositivity as the prevalence rates were not significantly different between male and female patients. However a higher seropositivity was observed in female patients than in male patients. This is in agreement with the findings previously reported in Malaysia (Ooi et al., 2002), Iran (Salimi et al., 2008) and Nigeria (Girei et al., 2010). The reason for this finding could be because women are always in contact with children.

Marital status did not affect the prevalence of the HPVB19 in this study. No statistically significant difference in the positivity was evident among the married patients and the unmarried individuals. This could be due to the fact that transmission of parvovirus infection is not through sexual route. A studyon blood donors in India did not find any association between HPVB19 and marital status (Kishore et al., 2010).

This study determined the effect of occupation, type of residence as well as number of people living in house on seropositivity of the viruses. This study observed a higher positivity among farmers, bike riders and unskilled labourers. This finding conforms to work of Kishore et al. (2010) among blood donors in India where high positivity was observed among unskilled labourers, could be explained by their poor living conditions such as poor housing and low educational levels. Outdoor activities could lead to more exposure and thus contact with infectious agents and could be a reason for higher prevalence among these occupational groups. High positivity observed in this study among full time housewives could also be due to the fact that women are always in contact with children both at home and outside the home. This finding does not conform to the work of Ujo et al.(2012) who did not find any association between occupation and HPVB19 among parents of children in their study (Ujo et al., 2012).

The relationship between socio-economic status and health outcome is well known (Alao et al., 2010). World Health Organization (1989) proposed a definition of standards of living “Income, occupation, standard of housing, sanitation, nutrition and the level of provision of health, educational, recreational, and other services may all be used individually as measures of socioeconomic status and collectively as an index of the standard of living.”(Kishore et al., 2010).

Education is a major factor influencing health status. The world map of literacy closely coincides with the maps of poverty, malnutrition, ill health, and high mortality rates. Studies have indicated that education, to some extent compensates the effects of poverty on health, irrespective of the availability of health facilities (Kishore et al., 2010). In this study the highest prevalence was observed among those without formal education and lowest prevalence was among the highly educated. The finding is consistent with findings of Kishore and colleagues conducted among blood donors and HPVB19 in India who also reported higher prevalence among illiterates, low educated group and lowest among the highly educated group (Kishore et al., 2010).

5.2 Conclusion

The findings in this study confirmed the presence of Hepatitis B infection infection in Kano State with sero-prevalence comparable to the rates found in various countries in the world. Sero-prevalence of HPVB19 among patients who have previosly been screened for the antigen was low leaving a large proportion (58%) of the population in Kano still susceptible to B19 infection. The study also showed that about 52% of women of childbearing age were still susceptible to HPVB19. This study also showed the effect of formal education, occupation and number of persons living in a house on seropositivity of individuals to HPVB19.

The prevalence of 8.5% obtained for the HBV showed that HBV infection is endemic in Kano and still poses as a public health problem which must be addressed.

It is very important, especially for health providers and policy makers, to recognize the health implication of these viruses in this area and design effective preventive programs.

5.3 Recommendations

In view of low prevalence of HPVB19, obtained in this study hence high susceptibility among population coupled with lack of data regarding the presence of HPV B19 among childbearing women in Kano, there is need for awareness on the virus to educate the public on the risk especially when pregnant.

In view of low prevalence of HPVB19 among pregnant women a prospective study is therefore recommended to investigate the prevalence of B19 parvovirus associated non immune hydrops and stillbirths in order to plan a national preventive approach.

There is also need to investigate the presence of HPVB19 among blood donors for probable inclusion as routine screening since Parvovirus B19 can be transmitted through blood products.

There is need for further investigation on the main risk factors associated with HBV infection in Kano state.

This study was hospital based, therefore there is need for a community based study, to detect the presence of current infection by detecting IgM and if possible molecular epidemiology researches as well as in the population in order to find out the persistence of HPVB19 DNA in tissues.

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